Higher Risk Of Myocardial Infarction Research Articles

Long-term outcomes after myocardial infarction in middle-aged and older patients with congenital heart disease-a nationwide study.

Aims We aimed to describe the risk of myocardial infarction (MI) in middle-aged and older patients with congenital heart disease (ACHD) and to evaluate the long-term outcomes after index MI in patients with ACHD compared with controls. Methods and results A search of the Swedish National Patient Register identified 17 189 patients with ACHD (52.2% male) and 180 131 age- and sex-matched controls randomly selected from the general population who were born from 1930 to 1970 and were alive at 40 years of age; all followed up until December 2017 (mean follow-up 23.2 ± 11.0 years). Patients with ACHD had a 1.6-fold higher risk of MI compared with controls [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.5–1.7, P < 0.001] and the cumulative incidence of MI by 65 years of age was 7.4% in patients with ACHD vs. 4.4% in controls. Patients with ACHD had a 1.4-fold increased risk of experiencing a composite event after the index MI compared with controls (HR 1.4, 95% CI 1.3–1.6, P < 0.001), driven largely by the occurrence of new-onset heart failure in 42.2% (n = 537) of patients with ACHD vs. 29.5% (n = 2526) of controls.Conclusion Patients with ACHD had an increased risk of developing MI and of recurrent MI, new-onset heart failure, or death after the index MI, compared with controls, mainly because of a higher incidence of newly diagnosed heart failure in patients with ACHD. Recognizing and managing the modifiable cardiovascular risk factors should be of importance to reduce morbidity and mortality in patients with ACHD.

Revisiting the use of the provocative acetylcholine test in patients with chest pain and nonobstructive coronary arteries: A five-year follow-up of the AChPOL registry, with special focus on patients with MINOCA

This study aimed to assess the angiographic characteristics, feasibility and safety of the provocative test with acetylcholine (AChT), and the influence on further treatment and prognosis of Middle European patients in 5-year follow-up, especially focusing on those with a history of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA). The AChPOL Registry was an ongoing prospective single-center registry that included patients undergoing AChT from December 2010 to March 2013 for further diagnostic evaluation of a suspicious variant angina or coronary microvascular spasm, based on the COVADIS criteria. AChT was injected in incremental doses of 25, 50, and 75µg into the right coronary artery and 25, 50, and 100 µg into the left coronary artery, and the patients were followed up for 5 years. We enrolled 211 patients in the AChPOL Registry. Their mean age was 60.5 ± 7.8 years, with women accounting for 67.8%. The median follow-up was 56 months. AChT revealed variant angina in 99 patients (46.9%) and coronary microvascular spasm in the remaining 72 patients (34.1%). In patients with variant angina, spasm was most frequently observed in the left anterior descending artery (89.9%) and was most frequently diffuse (61.6%). In the microvascular spasm subgroup, there was a significantly higher rate of recurrent chest pain requiring hospitalization in the follow-up than in AChT negative patients. Interestingly, patients with a history of MINOCA had higher rates of MI and recurrent chest pain requiring hospitalization in the follow-up. We showed that AChT was safe in Middle European patients. In the follow-up patients with microvascular spasm and a history of MINOCA had the highest risk of MI and recurrent chest pain requiring hospitalization.

NFKB1 gene rs28362491 ins/del variation is associated with higher susceptibility to myocardial infarction in a Chinese Han population

Myocardial infarction (MI), the leading cause of mortality and disability worldwide, is a disease in which multiple environmental and genetic factors are involved. Recently, researches suggested that insertion/deletion (ins/del) variation of NFKB1 gene rs28362491 is a functional polymorphism. In the present study, we aimed to explore the relation between variation of NFKB1 gene rs28362491 and MI by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) in 359 MI patients and 1085 control participants. Gensini score was used to evaluate the degree of coronary artery stenosis in MI patients. The plasma levels of interleukin-6 (IL-6), IL-8, malonaldehyde (MDA) and superoxide dismutase (SOD) were randomly measured by ELISA both in MI patients and control participants. We found that the detected frequencies of D allele (41.2% vs. 36.4%, P = 0.021) and DD genotype (17.5% vs. 12.0%, P = 0.022) were significantly higher in MI patients than in control participants. Compared with II or ID genotype carriers, the Gensini score in MI patients with DD genotype was 32–43% higher (both P < 0.001). Moreover, DD genotype carries had more diseased coronary arteries (P = 0.001 vs. II or ID genotype). Of note, IL-6 levels in MI patients carrying DD genotype were significantly higher than that in control participants and other genotype carriers in MI patients (both P < 0.05). In conclusion, NFKB1 gene rs28362491 DD genotype was associated with a higher risk of MI and more severe coronary artery lesion, which also had a potential influence on the level of inflammatory cytokine IL-6.

Hypertensive disorders of pregnancy and impact on in-hospital cardio-obstetric outcomes

Abstract Introduction Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity. However, short-term outcomes of HDP subgroups remain unknown. Methods Using the United States National Inpatient Sample database, all delivery hospitalizations between 2004 and 2014 with or without HDP (preeclampsia/eclampsia, chronic hypertension, superimposed preeclampsia on chronic hypertension and gestational hypertension) were analysed to examine the association between HDP and adverse in-hospital outcomes. Results We identified &amp;gt;44 million delivery hospitalizations, within which the prevalence of HDP increased from 8% to 11% over a decade with increasing comorbidity burden. Women with chronic hypertension have higher risks of myocardial infarction, peripartum cardiomyopathy, arrhythmia and stillbirth compared to women with preeclampsia. Out of all HDP subgroups, the superimposed preeclampsia population had the highest risk of stroke (OR 7.83, 95% CI 6.25, 9.80), myocardial infarction (OR 5.20, 95% CI 3.11, 8.69), peripartum cardiomyopathy (OR 4.37, 95% CI 3.64, 5.26), preterm birth (OR 4.65, 95% CI 4.48, 4.83), placental abruption (OR 2.22, 95% CI 2.09, 2.36), and stillbirth (OR 1.78, 95% CI 1.66, 1.92) compared to women without HDP. In conclusion, we are the first to evaluate chronic SH without superimposed preeclampsia as a distinct subgroup in HDP and show that women with chronic SH are at even higher risk of some adverse outcomes compared to women with preeclampsia. Conclusion The chronic hypertension population, with and without superimposed preeclampsia, is a particularly high risk group and may benefit from increased antenatal surveillance and the use of a prognostic risk assessment model incorporating HDP to stratify intrapartum care. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIHR

Utilization and outcomes of rotational atherectomy in Sweden

Abstract Aim To evaluate utilization and outcomes of rotational atherectomy (RA) using data from the Swedish Coronary and Angioplasty Registry (SCAAR) Methods We included 1476 patients with 2218 lesions who underwent RA from 2005 to 2016. To study temporal changes, the study period was divided into three equal time-periods, period A, B and C. Results Although the number of RA procedures increased 3-fold from 2005 to 2016, the rate of RA (of all PCI procedures) remained low (0.5% vs 1.2% in 2005 vs 2016). RA patients consisted a high-risk group, with advanced age and clustering of comorbidities. Over time, included patients were older and had a higher risk profile. Trans-radial access, drug eluting stent (DES) use and use of intravascular imaging significantly increased from period A to C whereas positioning of a temporary pacemaker or intra-aortic balloon pump declined. Unfractionated heparin became the main anticoagulant (52 vs 87%) and use of glycoprotein IIb/IIIa inhibitors declined (31 vs 12%, in period A vs C). Following RA, 11% of lesions were treated without stent (15 vs 15 vs 8%, in period A, B and C) (Rota-only). In lesions treated with a stent, a bare metal stent (BMS) was implanted in 39% vs 12% vs 2% and a new generation DES (N-DES) in 5 vs 75 vs 97% (period A vs B vs C) of lesions. The 3-year cumulative rate of restenosis was 6.7% (122 events), (11.1 vs 7.1 vs 4.1% in period A vs B vs C). As compared to DES, rota-only (adjusted HR 2.71; 95% CI 1.69- 4.36) and BMS (adjusted HR 3.63; 95% CI 2.27- 5.81) were associated with significantly higher risk for restenosis. First generation DES were associated with numerically higher but not significantly different risk for restenosis as compared to N-DES (adjusted HR 1.31; 95% CI 0.74- 2.31). The 3 year cumulative rate of major adverse cardiac events (MACE), including death, myocardial infarction (MI) or any restenosis was 30.6% (34.2 vs 31.4 vs 28.2%, in period A vs B vs C) and the corresponding numbers for all-cause mortality were 18.1% (18.9 vs 18.4 vs 17.0%). After adjustment for baseline characteristics and angiographic findings, RA in period A was associated with higher risk for MACE as compared to period C (adjusted HR 1.40; 95% CI 1.09- 1.79), due to higher risk for MI and restenosis. The difference disappeared when procedural characteristics, including DES use, were added to the model. The rate of major in-hospital complications was 7.0%, including in-hospital death 1.3%, periprocedural MI 2.8%, perforation 1.1%, cardiac tamponade 0.7%, stroke 0.2% and major bleedings 2.1%. We found no significant differences over time. Conclusion During the studied period, RA remained a rare procedure, utilised in a highly selected population. Over time a declining rate of restenosis and MI after RA was observed, a finding that appeared to be mainly driven by an increased use of DES. The rate of major in-hospital complication remained low. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific International

Cardiovascular risk of smoking in patients without obstructive coronary artery disease

Abstract Background Smoking increases risk of cardiovascular disease by increasing atherosclerosis and thrombogenesis. Purpose We examined the impact of smoking on cardiovascular risk in patients without obstructive coronary artery disease (CAD) after coronary angiography. Methods We conducted a cohort study in patients without obstructive CAD examined by coronary angiography from 2003–2016 in Western Denmark and no previous history of MI or coronary revascularization. Smokers were compared with non-smokers (former/never smokers) and with an age- and sex matched comparison group sampled from the Western Denmark general population without a history of CAD. The main outcome was myocardial infarction (MI). Other outcomes were ischemic stroke and death. Maximum follow-up was 10 years. Adjusted hazards ratios (aHRs) were estimated using Cox regression. Results We identified 46,462 patients without obstructive CAD, of whom 10,879 (23%) were active smokers and 35,583 (77%) were non-smokers at the time of angiography. Patients were matched with 234,648 individuals from the general population with no previous MI or coronary revascularization. Median follow-up was 7.0 years. Smokers had higher risks of MI (aHR 1.65, 95% CI: 1.41–1.93), ischemic stroke (aHR 1.49, 95% CI: 1.28–1.74), and death (aHR 1.77, 95% CI: 1.67–1.87) compared to non-smokers undergoing CAG. As shown in the Figure, the MI risk increased immediately after start follow-up and the curves continued to diverge. Compared to the general population, smokers without obstructive CAD had a similar risk of MI (aHR 0.96, 95% CI: 0.83–1.10), but an increased risk of ischemic stroke (aHR 1.36, 95% CI: 1.19–1.56) and death (aHR 1.49, 95% CI: 1.41–1.56), while non-smokers had reduced risks of MI (aHR 0.57, 95% CI: 0.51–0.63), ischemic stroke (aHR 0.85, 95% CI: 0.78–0.93), and death (aHR 0.78, 95% CI: 0.75–0.81). Conclusions In patients without obstructive CAD by coronary angiography, active smoking was associated with a 65% increased 10-year risk of MI compared to non-smokers, suggesting a prothrombotic effect of smoking. Compared to a general population, with unknown CAD and smoking status, smokers examined by CAG had a similar or higher risk of cardiovascular events despite the absence of CAD, while non-smokers had a lower risk. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital

The association of smoking to cardiovascular death differs according to age and sex following myocardial infarction complicated by heart failure or left ventricular dysfunction

Abstract Background Smoking is associated with higher morbidity and mortality following myocardial infarction (MI), but reports of the impact on cardiovascular (CV) death in aged and female patients experiencing MI complicated with left ventricular dysfunction or overt heart failure are limited. Methods In an individual patient data meta-analysis of high-risk MI patients, the association of smoking to CV death was investigated. Cox proportional hazard models exploring smoking status and risk according to age and sex were performed to study the relationship of smoking to independently adjudicated CV death endpoints. Results 28,771 patients from the CAPRICORN, EPHESUS, OPTIMAAL and VALIANT trials were assessed. 18,325 (64%) reported smoking (9185 (32%) current and 9051 (32%) past), 2662 (9%) were above ≥80 years and 8607 (30%) were women. Overall, using non-smokers as referent, the association of smoking to CV mortality was neutral (HR=1.07, 0.98 to 1.16, p=0.12 for active smoking and HR=1.10, 1.02 to 1.18, p=0.01 for past smoking). The associations for active and past smokers with outcome, adjusted for age and sex in the overall study sample and according to different age and sex categories, are presented in figure 1. In analyses that included interaction terms, the association for active smokers depended on age and sex; the risk of CV mortality was weakened in women (interaction HR=0.81, 0.69 to 0.96, p=0.01) and older age (interaction HR per 10 years increase=0.88, 0,82 to 0.95, p=0.001). In contrast, the association to CV death for past smokers was not modified by sex or age (p=0.86 and p=0.17 respectively). Conclusions The association of smoking to CV death differed according to age and sex in MI complicated with left ventricular dysfunction or overt heart failure. Significant association of active and/or past smoking with increased risk of CV death was mainly observed in the 60–69 years category. The underlying reasons of the lack of association of smoking with outcome in older patients in this specific context should be explored further in future studies. Figure 1 Funding Acknowledgement Type of funding source: None

Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the High-Risk-Myocardial-Infarction database

Abstract Background Sudden cardiac death (SCD) is responsible for 20–40% of mortality following acute myocardial infarction (AMI). The risk of SCD is even higher among patients with AMI complicated by heart failure (HF) (either clinically apparent HF or left ventricular dysfunction). The temporal relationship between an AMI complicated by HF and subsequent SCD and the association of non-fatal cardiovascular (CV) events following AMI with SCD has yet to be described. Purpose Among patients with AMI complicated by HF, we evaluated the probability and temporal association of subsequent non-fatal cardiovascular (CV) events (HF hospitalization, recurrent MI, or stroke) and SCD. Methods The High-Risk Myocardial Infarction (HRMI) database contains 28,771 patients with signs of HF or reduced LV ejection fraction (&amp;lt;40%) after AMI. Among patients with an AMI complicated by HF, we used adjudicated cause of death from the HRMI Database to identify: 1) the temporal distribution of SCD among patients following an index AMI; 2) the probability of having SCD following a non-fatal CV event following the index AMI. Results Median follow-up was 1.9 years. Mean age was 65.0±11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-year [py] and for SCD was 3.1 per 100py (40% of CV deaths). SCD rates were highest in the early period (&amp;lt;90 days) after AMI and decreased over time. Recurrent MI preceded 9.6% of SCD after a median time of 145 days; HF hospitalization preceded 17.0% of SCD after a median 144 days; and stroke preceded 2.7% of SCD after a median of 138 days (vs. non-sudden CV death: MI 46.6% at 1 days, HF hospitalization: 30.9% at 67 days, stroke 12.9% at 9 days). The incidence of SCD preceded by HF hospitalization was significantly higher than SCD without preceding HF hospitalization. Conclusion Among patients with AMI complicated by HF, SCD predominantly occurred in the early “high-risk” period after AMI; SCD rates decreased afterwards. Patients with non-fatal HF hospitalizations during follow-up may have a higher subsequent SCD risk. Preventing HF onset after MI may help decreasing SCD. Proportion of sudden cardiac death Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Lucien Award, McGill University

Myocardial Infarction after Kidney Transplantation: A Risk and Specific Profile Analysis from a Nationwide French Medical Information Database.

Introduction: Renal transplant recipients have a high peri-operative risk for cardiovascular events. The post-transplantation period also carries a risk of myocardial infarction (MI). Coronary artery disease (CAD) is a leading cause of death in these patients. We aimed to assess the risk of MI, the specific morbidity profile of MI after transplantation as well as the long-term prognosis after MI in renal transplantation (RT) patients regarding cardiovascular (CV) death and all-cause death. Methods: From a French national medical information database, all of the patients seen in French hospitals in 2013 with at least 5-years follow-up were retrospectively identified and patients without transplantation but with previous dialysis at baseline were excluded. There were 17,526 patients with RT and 3,288,857 with no RT. Results: Among these patients, 1020 in the RT group (5.8%), and 93,320 in the non-RT group (2.8%) suffered acute MI during a median follow-up of 5.4 years. After multivariable adjustment, risk of MI was higher in RT patients than in non-RT patients (HR 1.45, IC 95% 1.35–1.55). The mean age was 59.5 years for transplant patients with MI, and 70.6 years for the reference population with MI (p < 0.0001). MI patients with RT (vs. non RT patients) were more likely to have hypertension, diabetes dyslipidemia, and peripheral artery disease (76.0% vs. 48.1%, 38.7% vs. 25.2%, 33.2% vs. 23.2%, and 31.2% vs. 17.3%, respectively, p < 0.0001). Incidence of non ST-elevation MI (NSTEMI) was higher in RT patients while incidence of ST-elevation MI (STEMI) was higher in patients without RT. In unadjusted analysis, risk of all-cause death and CV death within the first month after MI were higher in patients without RT (18% vs. 11.1% p < 0.0001 and 12.3% vs. 7.8%, p < 0.0001, respectively). However, multivariable analysis indicated that risk of all-cause death was higher in patients with RT than in those with no RT (adjusted HR 1.15 IC 95% 1.03–1.28). Conclusions: MI is not an uncommon complication after RT (incidence of around 5.8% after 5 years). RT is independently associated with a 45% higher risk of MI than in patients without RT, with a predominance of NSTEMI. MI in patients with RT is independently associated with a 15% higher risk of all-cause death than that in patients with MI and no RT.

Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

Cardiovascular morbidity and mortality in patients with spondyloarthritis: A meta-analysis.

Cardiovascular (CV) risk and mortality associated with spondyloarthritis (SpA) remain controversial. Herein, we performed a meta-analysis of the latest large-scale population-based studies to demonstrate the elevated risk of CV disease and mortality in patients with SpA than in the general population. MEDLINE and EMBASE databases were searched systematically for population-based studies published between January 1997 and September 2019. Additional manual literature searches were also performed. All searches and data collection were performed independently by 2 reviewers. We calculated the risks of myocardial infarction (MI), stroke, and all-cause mortality in a meta-analysis and determined the risk ratios (RR) using the Mantel-Haenszel method. Among the 641 identified articles, 16 articles involving 18 cases met the inclusion criteria for our meta-analysis; these included 12 cases of ankylosing spondylitis, five cases of psoriatic arthritis, and 1 case of undifferentiated SpA. Our meta-analysis revealed a significantly high risk of MI (RR: 1.52; 95% CI: 1.29-1.80) and stroke (RR: 1.21; 95% CI: 1.0-1.47) in patients with SpA than in the general population. However, this increased risk was not significant in terms of all-cause mortality (RR: 1.23; 95% CI: 0.96-1.57). Our meta-analysis demonstrated that patients with SpA have a significantly increased risks of MI and stroke, but without a significant increase in the all-cause mortality, than that in the general population. The higher risk of CV in patients with SpA than that in the general population indicates the need for strict risk factor correction and disease management.

Impact of the Combinations of Allergic Diseases on Myocardial Infarction and Mortality

Allergic rhinitis (AR), atopic dermatitis (AD), and asthma, each by itself, are known to be associated with a higher risk of cardiovascular disease. Each of these diseases often coexists with one another, but the effect of combined allergic diseases on the long-term risk of myocardial infarction (MI) and mortality remains unknown. To evaluate the effects of various combinations of the allergic triad on the risk of MI and mortality. Adult allergic disease patients without prior MI were enrolled from the nationwide health check-up data provided by the Korean National Health Insurance Service in 2009. The primary and secondary end points were all-cause death and MI. A total of 9,548,939 individuals older than 20 years were selected for analysis. The prevalence of allergic diseases was 13.9% for AR, 0.4% for AD, and 2.7% for asthma. During a median 8.2 years of follow-up, 105,659 MIs and 298,769 deaths occurred. All allergic diseases were associated with an increased risk of MI (AR, adjusted hazard ratio [HRadjust], 1.11, 95% CI, 1.10-1.13; AD, HRadjust, 1.14, 95% CI, 1.06-1.24; asthma, HRadjust, 1.37, 95% CI, 1.33-1.40), whereas mortality risk was increased only for patients with AD (HRadjust, 1.15; 95% CI, 1.10-1.20) or asthma (HRadjust, 1.41; 95% CI, 1.39-1.43). Among the combinations of allergic diseases, patients with both AD and asthma had the highest risk of mortality (HRadjust, 1.71; 95% CI, 1.46-2.00) and MI (HRadjust, 1.57; 95% CI, 1.15-2.16). The results were significant after adjusting for demographic characteristics, comorbidities, socioeconomic status, and lifestyle factors. Patients with both AD and asthma have the highest risk of MI and mortality among all allergic disease combinations. Physicians should evaluate combinations of allergic conditions in allergic disease patients and promptly assess and manage their future risk of MI and mortality.

Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the high-risk myocardial infarction database.

Among patients with acute myocardial infarction (AMI) complicated by heart failure [HF; clinical HF or left ventricular (LV) systolic dysfunction], we explored the probability of subsequent non-fatal cardiovascular (CV) events and sudden cardiac death (SCD). The high-risk myocardial infarction (HRMI) database contains 28771 patients with signs of HF or reduced LV ejection fraction (<40%) after AMI. We evaluated the temporal association between SCD with preceding non-fatal CV event [HF hospitalization, recurrent myocardial infarction (MI), or stroke]. Median follow-up was 1.9 years. Mean age was 65.0 ± 11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-years and for SCD was 3.1 per patient-years (40% of CV deaths). The incidence of SCD preceded by HF hospitalization was greater than SCD without preceding HF hospitalization (P < 0.05). However, overall, SCD was less likely to be preceded by a non-fatal CV event compared to other causes of death: 9.6% of SCD events were preceded by an MI (vs. 46.6% for non-sudden CV death); 17.0% of SCD events were preceded with an HF hospitalization (vs. 25.4% for non-sudden CV death); and 2.7% of SCD events were preceded by stroke (vs.12.9% for non-sudden CV death). Among patients with AMI complicated by HF, SCD, compared with other causes of death, was less likely to be preceded by a non-fatal CV event. As patients are less likely to have preceding non-fatal CV events to alert the healthcare team of a possible impending SCD event, additional strategies for risk stratification for SCD are needed.

Modifiable Risk Among Medicare Beneficiaries Enrolled in the Million Hearts® Cardiovascular Disease Risk Reduction Model

Research ObjectiveThe Million Hearts ® Cardiovascular Disease (CVD) Risk Reduction Model aims to reduce CVD for those at highest 10‐year risk of myocardial infarction or stroke, but it is unclear how much risk is modifiable through key prevention strategies—blood pressure control, cholesterol control, smoking cessation, and aspirin therapy.Study DesignUsing clinical data and Medicare Part D pharmacy claims, we examined CVD risk factors, medication use, and 10‐year risk of myocardial infarction or stroke at baseline among Medicare beneficiaries enrolled in the Million Hearts Model. Among beneficiaries who met the model’s criteria for high (&gt;30%) or medium (15‐30%) CVD risk, we identified the proportion of risk that could be modified through risk factor control, using the Million Hearts® Longitudinal Atherosclerotic CVD Risk Assessment Tool to predict future risk after reaching target goals. Targets included reducing systolic blood pressure (SBP) below 130 mmHg, reducing low‐density lipoprotein below 70 mg/dL, universal smoking cessation, and aspirin use (where appropriate).Population Studied297,740 Medicare beneficiaries enrolled in the Million Hearts Model by intervention or control organizations.Principal FindingsIn both the intervention and control groups, eighteen percent of beneficiaries were at high risk for myocardial infarction or stroke and 40% were at medium risk. High SBP and other modifiable risk factors were common despite prevalent medication use at baseline, including antihypertensive use among 90% of high‐risk beneficiaries. We found that if beneficiaries reached targets, it would lead to a 15 percentage point absolute risk reduction in high‐risk beneficiaries, amounting to 39% of their CVD risk, and a six percentage point risk reduction in medium‐risk beneficiaries, amounting to 28% of their CVD risk. Among the prevention strategies, blood pressure control alone would result in the largest risk reduction for high‐risk beneficiaries, leading to an 11 percentage point risk reduction. Blood pressure and cholesterol control would each result in a two percentage point risk reduction for medium‐risk beneficiaries.ConclusionsThere is substantial room to reduce CVD risk among the Million Hearts Model’s target Medicare population. Blood pressure control has the greatest opportunity to reduce risk among the high‐risk group, and the greatest benefits may come from medication intensification, rather than initiation, as most beneficiaries are already on medication.Implications for Policy or PracticeWithout a substantial amount of modifiable risk, the Million Hearts Model could not achieve its intended goal of reducing the risk of heart attacks and stroke. These findings are encouraging that almost 40 percent of all CVD risk in the high‐risk target population could be reduced through the key Million Hearts prevention strategies. Blood pressure control, in particular, has a large potential to reduce CVD risk in the Million Hearts target population and likely more generally for higher risk Medicare beneficiaries across the United States.Primary Funding SourceCenters for Medicare and Medicaid Services.

Efficacy and safety of an antithrombotic regimen for atrial fibrillation patients with acute coronary syndrome or those undergoing percutaneous coronary intervention: a meta-analysis.

This study evaluated the benefit of dual therapy in reducing ischemic events in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing dual and triple therapies (oral anticoagulation plus aspirin and P2Y12 inhibitor) for AF patients with ACS or those undergoing PCI. The composite primary outcome included all-cause death, myocardial infarction (MI), stent thrombosis (ST), or stroke. Relative risk (RR) and the corresponding 95% confidence interval (CI) was used as the measure of effect size. Four RCTs with 10,969 patients were included. Dual therapy had a higher event rate of primary outcome than triple therapy (RR, 1.15; 95%CI, 1.03–1.28; P<0.0001). Dual therapy was associated with significantly higher MI risk, insignificantly higher ST risk, and significantly lower major bleeding risk than triple therapy (RR1.23, 95%CI 1.01–1.49, P = 0.036; RR 1.43, 95 %CI 0.98–2.09, P = 0.064; and RR0.58, 95%CI 0.45–0.76, P<0.0001, respectively). Dual antithrombotic therapy was associated with higher ischemic risk but lower major bleeding risk than triple therapy. The data suggest that antithrombotic regimens should be based on tradeoffs between ischemia and bleeding risk.

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics.

Inhibition of sclerostin is a therapeutic approach to lowering fracture risk in patients with osteoporosis. However, data from phase 3 randomized controlled trials (RCTs) of romosozumab, a first-in-class monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events, and regulatory agencies have issued marketing authorizations with warnings of cardiovascular disease. Here, we meta-analyze published and unpublished cardiovascular outcome trial data of romosozumab and investigate whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. Meta-analysis of up to three RCTs indicated a probable higher risk of cardiovascular events with romosozumab. Scaled to the equivalent dose of romosozumab (210 milligrams per month; 0.09 grams per square centimeter of higher bone mineral density), the SOST genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab) and with a higher risk of myocardial infarction and/or coronary revascularization and major adverse cardiovascular events. The same variants were also associated with increased risk of type 2 diabetes mellitus and higher systolic blood pressure and central adiposity. Together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.

Cardiac magnetic resonance in cocaine-induced myocardial damage: cocaine, heart, and magnetic resonance.

The use of cocaine constitutes a major health problem. Cocaine use is associated with acute and chronic complications that might involve any system, the most common being the cardiovascular system. The precise incidence of cocaine-induced cardiomyopathy remains mysterious and probably underreported. Cocaine use should be considered in young patients presenting with chest pain or heart failure without other underlying risk factors. Cocaine-related cardiovascular complications can be acute or chronic and include ischemic and non-ischemic events. Frequent cocaine users have a seven-fold higher risk of myocardial infarction. In addition to its ischemic effects, other cardiovascular complications of cocaine use and abuse are hypertensive crises, aortic dissection or aortic rupture, cerebral hemorrhage, arrhythmias and sudden cardiac death, myocarditis, dilated cardiomyopathy, heart failure, and endocarditis. The mechanism of cocaine's cardiovascular toxicity relates to its sympathomimetic effect, to the block of voltage-dependent K+ and Na2+ channels, and a hypersensitivity reaction to drug or contaminants, such as amphetamine, sugars, or talc. Cardiac magnetic resonance (CMR) can provide a valuable assessment of cocaine-induced myocardial damage both in acute and chronic cardiac complications: it gives prognostic information in clinically relevant settings, and it identifies silent myocardial damage in asymptomatic patients. Indeed, CMR study should be considered in symptomatic cocaine users to assess the extent and evolution of myocardial injury. Furthermore, it was suggested to repeat CMR after 4-8months of appropriate management to evaluate myocardial response to abstinence and medical therapy.

SUN-620 Gender Difference in the Outcome of Patients with Diabetes Admitted for Hyperosmolar Hyperglycemia. from the National Inpatient Sample

Objective: There is paucity of literature on the impact of gender on outcomes of hyperosmolar hyperglycemic state (HHS) among adult patients with diabetes. The aim of this study was to evaluate the effect of gender on the outcome of these patients. Methodology: The National Inpatient Sample (NIS) was queried for all patients who were admitted with a diagnosis of hyperosmolar hyperglycemic state (HHS) during the years 2005-2014. The primary outcomes of the study were all-cause mortality, acute myocardial infarction (MI), and acute stroke. The secondary outcomes were acute kidney injury (AKI), rhabdomyolysis, acute respiratory failure (ARF), need for mechanical ventilation (MV), length of stay (LOS), and total cost of stay. Results: Overall, 188,725 patients were admitted for HHS. Mean age of males was 53.7, standard error of the mean (SEM: 0.13), and of females was 58.5 (SEM: 0.15), p<0.001. Females were (43.9%), Caucasians were 37.4% while African Americans were 35.2%. Total mortality was 1.1%, MI was 1.3% and stroke was 1.1%. Most common secondary outcome was AKI seen in 31.3% followed by ARF seen in 2.9% of total. The mean cost was 7887 $ (SEM: 84.6) and mean LOS was 4.1 days (SEM: 0.03). Both males and females had equivalent rates of mortality, stroke, ARF and need for mechanical ventilation. Compared to males, females had significantly higher risk for MI 1.6% vs 1.1%, p<0.001, lower risk for AKI 29.3% vs 32.9%, p<0.001, lower risk for rhabdomyolysis 1.1% vs 2%, p<0.001 and higher LOS 4.3 vs 3.9 days, p<0..01 and higher total costs 8165.6 $ vs 7669.3 $, p < 0.001. On multivariable analysis, female gender was independently predictive for higher risk for MI with adjusted odds ratio (aOR) 1.34 [95%CI: 1.08-1.67] p=0.01 and lower risk for rhabdomyolysis with aOR 0.52 [95%CI: 0.42-0.63] p<0.001 and lower risk for AKI with aOR 0.74 [95%CI: 0.7-0.78] p<0.001. In addition, female gender correlated with higher cost and length of stay. Conclusion: Females with hyperosmolar hyperglycemic state are at higher risk for MI and lower risk for AKI and rhabdomyolysis.

Blood Pressure-Lowering Profiles and Clinical Effects of Angiotensin Receptor Blockers Versus Calcium Channel Blockers.

Blood pressure-lowering drugs have different blood pressure-lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg (P values <0.0001). The higher risks of myocardial infarction and stroke in the valsartan group was attenuated after adjustment for mean and variability of systolic blood pressure, from HR 1.19 (95% CI, 1.02-1.39) to 1.11 (0.96-1.30) and from HR 1.13 (0.96-1.33) to 1.00 (0.85-1.18), respectively. The lower risk of congestive heart failure in the valsartan group was accentuated after adjustment, from HR 0.86 (0.74-1.00) to 0.76 (0.65-0.89). A smaller effect was seen on risk of death, from 1.01 (0.92-1.12) to 0.94 (0.85-1.04). In conclusion, the higher risks of myocardial infarction and stroke in patients randomized to valsartan versus amlodipine were related to the drugs' different blood pressure modulating profiles. The risk of congestive heart failure with valsartan was lower, independent of the less favorable blood pressure modulating profile.

Acute Migraine Prescription Patterns Vary by Baseline Cardiovascular Risk and Clinical Characteristics: A Real-World Evidence Study.

IntroductionMigraine is a debilitating neurological disease and one of the most common disorders in the world. Although the triptans, potent 5-HT1B/1D receptor agonists, are an effective and widely used acute treatment of migraine, few studies have assessed how their cardiovascular risk warnings could impact prescription patterns. This study characterized cardiovascular risk factors and other aspects of people with migraine in real-world settings and confirmed patterns of acute migraine care.MethodsThis retrospective study included five cohorts: people with migraine prescribed acute treatments [triptans, opiates, prescription nonsteroidal anti-inflammatory drugs (NSAIDs)], untreated people with migraine, and individuals without migraine diagnosis. Baseline demographic and clinical characteristics were used to develop and validate a 1-year myocardial infarction (MI) risk prediction model among untreated people with migraine. This validated prediction model generated disease risk scores (DRSs) for MI among untreated cohorts.ResultsPatients in the study included 436,642 prescribed a triptan, 55,234 prescribed opiates, and 334,152 prescribed NSAIDs; as well as 1,168,212 untreated persons with migraine and 11,735,009 nonmigraine participants. Those prescribed triptans were younger, had fewer cardiovascular risk factors and hospitalizations, and lower concomitant medication use than those in the NSAID and opiate cohorts. The distribution of the DRS showed that compared to patients prescribed NSAIDs (4.2%) or opiates (3.5%), a smaller proportion of patients prescribed triptans (1.3%) were at high risk for MI at 1 year (> 10%).ConclusionPeople with migraine who had more cardiovascular risk factors and greater 1-year MI risk score were disproportionately prescribed opiates and NSAIDs compared to triptans. Future research should explore unmet needs for patients with disorders for which triptan therapy is contraindicated.